Aspergillus fumigatus (A. fumigatus) is a ubiquitous spore-producing mold that can cause a diverse spectrum of human diseases, ranging from allergic hypersensitivity and non-invasive colonization to life-threatening invasive infections. Invasive aspergillosis (IA) is the most devastating disease caused by this fungus in immunocompromised patients. Despite new anti-fungal drugs, morbidity and mortality continue to be unacceptable high and invasive aspergillosis has become a major cause of infection-related mortality in hematopoietic stem cell recipients.
Although we routinely inhale several hundreds or thousands of A. fumigatus conidia per day, immune-competent individuals are efficiently protected by innate and adaptive immune mechanisms. Lung-resident alveolar macrophages and neutrophils ingest and kill A fumigatus conidia and germlings and recruit other immune cells by secretion of pro-inflammatory cytokines. There is increasing evidence that CD4+ T cells orchestrate the anti-fungal immune response. In mouse models, monocytes and dendritic cells have been shown to prime A. fumigatus-specific CD4+ T cell responses that migrate to the airways. Adoptive transfer of A. fumigatus-specific IFN-γ producing T cells protected mice from invasive fungal disease and correlated with survival of IA patients. In accordance with the idea that humans are constantly confronted with fungal antigens it was recently shown that a small population of A. fumigatus-specific T cells is indeed consistently present in healthy donors (Bacher et al J Immunol 2013, Bacher et al Mucosal Immunol 2013). In IA patients, the frequencies of A. fumigatus-reactive T cells are strongly increased (unpublished observation) indicating the involvement of specific CD4+ T cells in antifungal immune defense.
Therefore, approaches supporting fungus-specific CD4+ T cells in immuno-compromised persons, e.g. by vaccination or adoptive T cell transfer seem to be promising for pre-emptive or therapeutic intervention against invasive fungal infections. However, in order to develop efficient immunotherapies or immunodiagnostic tools, a crucial first step is to define the antigen specificity of the human CD4+ T cells in vivo. Due to the complexity of the A. fumigatus proteome it is currently not known against which fungal antigens human T cells predominantly react and which T cell specificities are protective. The A. fumigatus genome contains several thousand open reading frames, encoding potential antigenic proteins. Bacher et al (J Immunol 2013 & Mucosal Immunol 2013) disclosed a highly specific and sensitive assay to enumerate and characterize antigen-specific CD4+ T cells directly ex vivo based on CD154+pre-enrichment (Antigen-Reactive T cell Enrichment, ARTE). There is a need in the art for the identification of immunogenic antigens of Aspergillus fumigatus allowing the detection of Aspergillus fumigatus-specific T cells and/or which are useful for immunotherapy or immunodiagnostics.